Alzheimer's disease (AD) (J. Med. Chem. 46, 2279, 2003) is a chronic neuro degenerative disorder, which finds severe behavioral abnormalities and loss of cognitive ability. Alzheimer's disease is associated with cerebral cholinergic hypo function and characterized by plaques of the amyloid β-peptide, neurofibrillary tangles and degeneration or atrophy of the basal forebrain cholinergic neurons. The loss of forebrain cholinergic cells results reduction in acetylcholine, which plays an important role in the cognitive impairment associated with Alzheimer's disease. One of the most promising approaches for the treatment of Alzheimer's disease is to increase in the levels of acetyl choline by inhibition of acetycholinesterase.
Several approaches have been developed for the treatment of Alzheimer's disease by inhibiting the AChE. The most used AChE inhibitors are Galanthamine, donepezil, rivastigmine, tacrine and 2H-3,4-tetrahydroquinazoline-2-one & 2H-3,4-tetrahydro quinazoline-2,4-dione (U.S. Pat. No. 5,504,088, 1996) were also reported.
Pyrano coumarins, furo coumarins and substituted coumarins are natural compounds possessing biological activities like purgative (J. Indian. Chem. Soc. Vol 66, 66, 1989), insecticidal (Jpn. Appl. 7 973 12, 1977; Chem. Abstr Vol 91, p 152771u, 1977), antimicrobial (Chem. Abstr. Vol 56, 1835b, 1962), anti feedant (J. Agric. Food. Chem. Vol 37, 1435, 1989), antiulcer (Fitoterapia Vol 68, 410, 1997; Chem. Abstr Vol 128, 268242j, 1998), anti cancer (J. Nat. Prod. Vol 57, 518, 1994) and anti HIV (U.S. Pat. No. 5,637,589; Chem. Abstr. Vol 127, 104326t, 1997). Coumarin derivatives were also exhibited monoamine oxidase (MAO-A& B) inhibitory properties (J. Med. Chem 43, 4747, 2000, J. Med. Chem 44, 3195, 2001, Arkivoc, 272, 2004).
The present invention relates to the compounds of natural sources (±) Marmesin, Columbianetin (Phytochemistry, Vol 39(6), 1347, 1995) Dihydroxanthyletin (Phytochemistry, Vol 34(3), 819, 1993), coumarin derivatives of 7-allyloxy coumarin, 7-benzyloxy coumarin, 7-methoxy coumarin, 7-acetyloxy coumarin, 4-methyl-7-hydroxy coumarin and 4-methyl-7-acetyloxy coumarin are potent highly selective towards the AChE in vitro and in vivo. These compounds are highly effective for the treatment and prevention of AChE.